A team from the Institute of Neurosciences of the University of Barcelona (UBneuro) has designed and validated in animal models an innovative compound with a pioneering mechanism of action for the treatment of Alzheimer’s disease. Unlike current drugs, which mainly remove beta-amyloid plaques that accumulate in the brain, this new experimental drug reprogrammes the neuronal epigenome by correcting alterations in gene expression that contribute to the progression of the disease. The results of this study, published in Molecular Therapy, open the door to an epigenetic-based therapeutic strategy to fight Alzheimer’s disease.
“The compound FLAV-27 represents an innovative and promising approach to Alzheimer’s disease, with the potential to modify the disease process, as it acts not only on its symptoms or a single pathological biomarker, but directly on its underlying molecular mechanisms,” says Aina Bellver, a researcher at the UB Institute of Neurosciences (UBneuro) and first author of the paper.
The study was led by Christian Griñán and Mercè Pallàs, UBneuro researchers and Professors from the Faculty of Pharmacy and Food Sciences. Th work was performed with the participation of researchers from the CIBER Area for Neurodegenerative Diseases (CIBERNED), as well as the UB Institute of Biomedicine (IBUB), the Institute of Nutrition and Food Safety (INSA-UB), the August Pi i Sunyer Biomedical Research Institute (IDIBAPS) and other national and international institutions.
Genetic switches near the FTO locus may enable hibernators’ extreme metabolic resilience and could inspire future treatments for human metabolic and age-related diseases.
In this Research article, Benjamin D. Philpot & team establish a multimodal dual-reporter mouse that accelerates AngelmanSyndrome therapeutic development through scalable cell-based screening, high-resolution whole-brain mapping, non-invasive live imaging, and sorting neurons with unsilenced paternal Ube3a.
2Animal Models Core.
3Department of Genetics, and.
4Carolina Institute for Developmental Disabilities, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Sabine Hossenfelder, Ivette Fuentes and James Ladyman discuss the scaling laws of the universe and the fundamental nature of reality.
Is the universe one thing, or many things?
With a free trial, you can watch the full debate NOW at https://iai.tv/video/the-one-and-the–… central question in ancient Greek philosophy was the problem of the One and the Many. It is a question that has echoed across Western culture and is still with us today. Should we see the world as a coherent whole or a multitude of separate parts? The puzzle is that we need both the whole and the parts, but an explanation of the relationship between them has proved problematic and perhaps unknowable. In contemporary physics, the parts are the teeming world of particle physics, and these should make up the cosmological world of the universe as a whole and the overall framework of Einsteinian space-time. But as yet we have not been able to combine the two coherently. Is looking at the universe from the small scale and the large always going to be incompatible? Does it mean a theory of everything is an illusion and the attempt to combine quantum mechanics and Einstein’s general relativity a forlorn project? Or is the parallel with the ancient Greek puzzle accidental and the current challenge one that might be overcome? #quantumphysics #universe #philosophy #fundamentalunits #theoryofeverything Sabine Hossenfelder is a theoretical physicist and acclaimed science communicator, known for her sharp critiques of the scientific mainstream. She is also a best-selling author and YouTuber. Ivette Fuentes is a theoretical quantum physicist at the University of Southampton and Emmy Fellow at the University of Oxford. James Ladyman is a philosopher of science at the University of Bristol. He is best known for his book Every Thing Must Go, calling for a metaphysics grounded in physics and complexity science. Hosted by Jack Symes. 00:40 James Ladyman on the different notions of scale 02:39 Sabine Hossenfelder on energy in the universe 05:19 Ivette Fuentes on unifying quantum mechanics and general relativity 09:00 Is the universe “One” or “Many”? 17:15 Particles are not fundamental The Institute of Art and Ideas features videos and articles from cutting edge thinkers discussing the ideas that are shaping the world, from metaphysics to string theory, technology to democracy, aesthetics to genetics. Subscribe today! https://iai.tv/subscribe?utm_source=Y… For debates and talks: https://iai.tv For articles: https://iai.tv/articles For courses: https://iai.tv/iai-academy/courses.
A central question in ancient Greek philosophy was the problem of the One and the Many. It is a question that has echoed across Western culture and is still with us today. Should we see the world as a coherent whole or a multitude of separate parts? The puzzle is that we need both the whole and the parts, but an explanation of the relationship between them has proved problematic and perhaps unknowable. In contemporary physics, the parts are the teeming world of particle physics, and these should make up the cosmological world of the universe as a whole and the overall framework of Einsteinian space-time. But as yet we have not been able to combine the two coherently.
Is looking at the universe from the small scale and the large always going to be incompatible? Does it mean a theory of everything is an illusion and the attempt to combine quantum mechanics and Einstein’s general relativity a forlorn project? Or is the parallel with the ancient Greek puzzle accidental and the current challenge one that might be overcome?
Jamaluddin et al. investigated how the MRAP2 accessory protein enhances signaling by three appetite-regulating GPCRs. MRAP2 disrupts GPCR oligomerization to form interactions, and its cytoplasmic region is essential for signaling. MRAP2 variants modulate receptor constitutive activity, enhance internalization, and reduce signaling, contributing to weight gain and hyperglycemia observed in humans.
The researchers present the first integrative catalogue of 267 cullin–RING substrate receptors, of which 93 are linked to germline disorders.
The most frequent substrate receptor (SR)-related diseases are neurodevelopmental, neuromuscular, and congenital organ/skeletal syndromes.
Disease associations are shaped by substrate context rather than tissue enriched expression.
Pathogenicity arises through altered degron recognition, disrupted complex assembly, dosage imbalance, or ubiquitin–proteasome system-independent functions.
Distinct variants in the same SR can yield divergent phenotypes, reflecting dosage sensitivity and developmental context.
Patient alleles inform diagnosis and therapeutic strategies, positioning SRs as central nodes connecting proteostasis, rare-disease genetics, and targeted protein degradation. sciencenewshighlights ScienceMission https://sciencemission.com/Cullin%E2%80%93RING-receptors
Priti Agarwal, Ronen Zaidel-Bar et al. define the stage-specific gene expression programs of a leader cell that drives collective tissue invasion during organ development, identifying membrane trafficking as a central regulator of leader cell behavior.
Migration.
Collective cell invasion underlies organ development, epithelial repair, and cancer metastasis. “Leader cells” remodel ECM, sense guidance cues, reorganize their cytoskeleton, and coordinate follower cells, but the molecular programs enabling these functions remain unclear. Here, we present a stage-specific transcriptomic dataset of the Caenorhabditis elegans gonadal leader cell, the distal tip cell (DTC), which invades basement membrane and guides germ cells to form U-shaped gonadal arms. Comparing invasive larval-stage DTCs with noninvasive adult-stage DTCs defines the molecular signature of an actively invading leader cell in vivo. Our dataset recapitulates known regulators of gonad morphogenesis and reveals numerous uncharacterized genes with potential roles in leader cell activity. Demonstrating dataset utility, we identify vesicular trafficking proteins enriched in invading DTCs and demonstrate their importance for gonad development using endogenous tagging and DTC-specific RNAi. We also catalog diverse DTC-specific knockdown phenotypes. This resource establishes a molecular framework for leader cell activity and a platform to investigate conserved mechanisms of invasive migration.
A new form of in vivo CAR-T therapy kills leukemia, multiple myeloma, and sarcoma in mice, opening the door to a future off-the-shelf cancer treatment without chemotherapy.
For years, one of the most powerful weapons against certain blood cancers, called CAR-T therapy, has required an elaborate process: Doctors extract a patient’s immune cells, ship them to a specialized facility where they’re genetically reprogrammed to fight cancer, then ship them back for infusion into the patient’s bloodstream. This has revolutionized cancer treatment, but the time and expense place it out of reach for thousands of patients.
Now, scientists at UC San Francisco and UC Berkeley have developed a method to precisely reprogram these cancer-fighting cells directly inside the body, potentially eliminating the barriers that have kept this life-saving therapy out of reach for many patients around the world.
Here, Tobias B. Huber & team use a state-of-the-art, tour de force experimental design to show LSD1 regulates kidney development, and its dysfunction disrupts key kidney cells, leading to cyst formation in mouse and organoid models.
The image shows severe structural changes in the adult mouse kidney with loss of KDM1a. Nephrology.
4Faculty of Biology, Albert Ludwigs University of Freiburg, Freiburg, Germany.
5Institute of Medical Bioinformatics and Systems Medicine and.
6Institute of Surgical Pathology, Faculty of Medicine, Medical Center — University of Freiburg, Freiburg, Germany.
